tbuckley/cabot-search huggingface dataset:
Local translation in microglial processes is required for efficient phagocytosis
Authors: Michael J. Vasek, Shayna M. Mueller, Stuart B. Fass, Jelani D. Deajon-Jackson, Yating Liu, Haley W. Crosby, Sarah K. Koester, Jiwon Yi, Qingyun Li, Joseph D. Dougherty
Journal: Nature Neuroscience (2023)
Pulsed antibiotic treatments of gnotobiotic mice manifest in complex bacterial community dynamics and resistance effects
Authors: Philipp C. Münch, Claudia Eberl, Simon Woelfel, Diana Ring, Adrian Fritz, Simone Herp, Iris Lade, Robert Geffers, Eric A. Franzosa, Curtis Huttenhower, Alice C. McHardy, Bärbel Stecher
Journal: Cell Host & Microbe (2023)
A Review of Image-Based Food Recognition and Volume Estimation Artificial Intelligence Systems
Authors: Fotios S. Konstantakopoulos, Eleni I. Georga, Dimitrios I. Fotiadis
Journal: IEEE Reviews in Biomedical Engineering (2023)

The daily healthy diet and balanced intake of essential nutrients play an important role in modern lifestyle. The estimation of a meal's nutrient content is an integral component of significant diseases, such as diabetes, obesity and cardiovascular disease. Lately, there has been an increasing interest towards the development and utilization of smartphone applications with the aim of promoting healthy behaviours. The semi - automatic or automatic, precise and in real-time estimation of the nutrients of daily consumed meals is approached in relevant literature as a computer vision problem using food images which are taken via a user's smartphone. Herein, we present the state-of-the-art on automatic food recognition and food volume estimation methods starting from their basis, i.e., the food image databases. First, by methodically organizing the extracted information from the reviewed studies, this review study enables the comprehensive fair assessment of the methods and techniques applied for segmenting food images, classifying their food content and computing the food volume, associating their results with the characteristics of the used datasets. Second, by unbiasedly reporting the strengths and limitations of these methods and proposing pragmatic solutions to the latter, this review can inspire future directions in the field of dietary assessment systems.
Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis
Authors: Melanie H. Smith, Vianne R. Gao, Preethi K. Periyakoil, Alejandro Kochen, Edward F. DiCarlo, Susan M. Goodman, Thomas M. Norman, Laura T. Donlin, Christina S. Leslie, Alexander Y. Rudensky
Journal: Nature Immunology (2023)

Abstract Inflammation of non-barrier immunologically quiescent tissues is associated with a massive influx of blood-borne innate and adaptive immune cells. Cues from the latter are likely to alter and expand activated states of the resident cells. However, local communications between immigrant and resident cell types in human inflammatory disease remain poorly understood. Here, we explored drivers of fibroblast-like synoviocyte (FLS) heterogeneity in inflamed joints of patients with rheumatoid arthritis using paired single-cell RNA and ATAC sequencing, multiplexed imaging and spatial transcriptomics along with in vitro modeling of cell-extrinsic factor signaling. These analyses suggest that local exposures to myeloid and T cell-derived cytokines, TNF, IFN-γ, IL-1β or lack thereof, drive four distinct FLS states some of which closely resemble fibroblast states in other disease-affected tissues including skin and colon. Our results highlight a role for concurrent, spatially distributed cytokine signaling within the inflamed synovium.
The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap
Authors: Keenan A. Walker, Lydia M. Le Page, Niccolò Terrando, Michael R. Duggan, Michael T. Heneka, Brianne M. Bettcher
Journal: Molecular Neurodegeneration (2023)

Abstract Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon that has been identified as a risk factor for Alzheimer’s disease. While the role of chronic peripheral inflammation has been well characterized in the context of dementia and other age-related conditions, less is known about the neurologic contribution of acute inflammatory insults that take place outside the central nervous system. Herein, we define acute inflammatory insults as an immune challenge in the form of pathogen exposure (e.g., viral infection) or tissue damage (e.g., surgery) that causes a large, yet time-limited, inflammatory response. We provide an overview of the clinical and translational research that has examined the connection between acute inflammatory insults and Alzheimer’s disease, focusing on three categories of peripheral inflammatory insults that have received considerable attention in recent years: acute infection, critical illness, and surgery. Additionally, we review immune and neurobiological mechanisms which facilitate the neural response to acute inflammation and discuss the potential role of the blood–brain barrier and other components of the neuro-immune axis in Alzheimer’s disease. After highlighting the knowledge gaps in this area of research, we propose a roadmap to address methodological challenges, suboptimal study design, and paucity of transdisciplinary research efforts that have thus far limited our understanding of how pathogen- and damage-mediated inflammatory insults may contribute to Alzheimer’s disease. Finally, we discuss how therapeutic approaches designed to promote the resolution of inflammation may be used following acute inflammatory insults to preserve brain health and limit progression of neurodegenerative pathology.
Burden of disease attributable to unsafe drinking water, sanitation, and hygiene in domestic settings: a global analysis for selected adverse health outcomes
Authors: Jennyfer Wolf, Richard B Johnston, Argaw Ambelu, Benjamin F Arnold, Robert Bain, Michael Brauer, Joe Brown, Bethany A Caruso, Thomas Clasen, John M Colford, Joanna Esteves Mills, Barbara Evans, Matthew C Freeman, Bruce Gordon, Gagandeep Kang, Claudio F Lanata, Kate O Medlicott, Annette Prüss-Ustün, Christopher Troeger, Sophie Boisson, Oliver Cumming
Journal: The Lancet (2023)

Assessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels.
Associations between residential greenspace exposure and mortality in 4 645 581 adults living in London, UK: a longitudinal study
Authors: Samantha Hajna, Vahé Nafilyan, Steven Cummins
Journal: The Lancet Planetary Health (2023)

BackgroundUrban greenspaces could reduce non-communicable disease (NCD) risk. The links between greenspaces and NCD-related mortality remain unclear. We aimed to estimate associations between residential greenspace quantity and access and all-cause mortality, cardiovascular disease mortality, cancer mortality, respiratory mortality, and type 2 diabetes mortality.MethodsWe linked 2011 UK Census data of London-dwelling adults (aged ≥18 years) to data from the UK death registry and the Greenspace Information for Greater London resource. We calculated percentage greenspace area, access point density (access points per km2), and distance in metres to the nearest access point for each respondent's residential neighbourhood (defined as 1000 m street network buffers) for greenspaces overall and by park type using a geographic information system. We estimated associations using Cox proportional hazards models, adjusted for a range of confounders.FindingsData were available for 4 645 581 individuals between March 27, 2011, and Dec 31, 2019. Respondents were followed up for a mean of 8·4 years (SD 1·4). All-cause mortality did not differ with overall greenspace coverage (hazard ratio [HR] 1·0004, 95% CI 0·9996–1·0012), increased with increasing access point density (1·0076, 1·0031–1·0120), and decreased slightly with increasing distance to the nearest access point (HR 0·9993, 0·9987–0·9998). A 1 percentage point (pp) increase in pocket park (areas for rest and recreation under 0·4 hectares) coverage was associated with a decrease in all-cause mortality risk (0·9441, 0·9213–0·9675), and an increase of ten pocket park access points per km2 was associated with a decreased respiratory mortality risk (0·9164, 0·8457–0·9931). Other associations were observed, but the estimated effects were small (eg, all-cause mortality risk for increases of 1 pp in regional park area were 0·9913, 0·9861–0·9966 and increases of ten small open space access points per km2 were 1·0247, 1·0151–1·0344).InterpretationIncreasing the quantity of, and access to, pocket parks might help mitigate mortality risk. More research is needed to elucidate the mechanisms that could explain these associations.FundingHealth Data Research UK (HDRUK).
National income and macro-economic correlates of the double burden of malnutrition: an ecological study of adult populations in 188 countries over 42 years
Authors: Satheesh Seenivasan, Debabrata Talukdar, Anish Nagpal
Journal: The Lancet Planetary Health (2023)

The double burden of malnutrition (DBM) represents a growing global challenge with adverse health and economic consequences. We aimed to investigate the associative roles of national income (gross domestic product per capita [GDPPC]) and macro-environmental factors on the DBM trends among national adult populations.In this ecological study we assembled extensive historical data on GDPPC from the World Bank World Development Indicators database and population-level DBM data of adults (aged ≥18 years) from the WHO Global Health Observatory database in 188 countries over 42 years (1975-2016). In our analysis, a country was considered to have the DBM in a year when adult overweight (BMI ≥25·0 kg/m2) and underweight (BMI <18·5 kg/m2) prevalence was each 10% or more in that year. We used a Type 2 Tobit model to estimate the association of GDPPC and selected macro-environmental factors (globalisation index, adult literacy rate, female share in the labour force, share of agriculture in the national gross domestic product [GDP], prevalence of undernourishment, and percentage of principal display area mandated to be covered by health warnings on cigarette packaging) with DBM in 122 countries.We find a negative association between GDPPC and the likelihood of a country having the DBM. However, conditional on its presence, DBM level exhibits an inverted-U shaped association with GDPPC. We found an upward shift in DBM levels from 1975 to 2016 across countries at the same level of GDPPC. Among the macro-environmental variables, share of females in the labour force and share of agriculture in the national GDP are negatively associated with DBM presence in a country, whereas the prevalence of undernourishment in the population is positively associated. Further, globalisation index, adult literacy rate, share of females in the labour force, and health warnings on cigarette packaging are negatively associated with DBM levels in countries.DBM level in national adult populations rises with GDPPC until US$11 113 (in 2021 constant dollar terms) and then starts declining. Given their current GDPPC levels, most low-income and middle-income countries are thus unlikely to have a decline in the DBM levels in the near future, ceteris paribus. Those countries will also be expected to experience a higher DBM level at similar levels of national income than were historically experienced by the current high-income countries. Our findings point to a further intensification of the DBM challenge in the near future for the low-income and middle-income countries as they continue to have income growth.None.
Antithrombotic Treatment in Patients With Hemophilia: an EHA-ISTH-EAHAD-ESO Clinical Practice Guidance
Authors: Roger E.G. Schutgens, Victor Jimenez-Yuste, Miguel Escobar, Anna Falanga, Bruna Gigante, Robert Klamroth, Riitta Lassila, Frank W.G. Leebeek, Michael Makris, Tarek Owaidah, Michelle Sholzberg, Andreas Tiede, David J. Werring, H. Bart van der Worp, Jerzy Windyga, Giancarlo Castaman
Journal: HemaSphere (2023)

Cardiovascular disease is an emerging medical issue in patients with hemophilia (PWH) and its prevalence is increasing up to 15% in PWH in the United States. Atrial fibrillation, acute and chronic coronary syndromes, venous thromboembolism, and cerebral thrombosis are frequent thrombotic or prothrombotic situations, which require a careful approach to fine-tune the delicate balance between thrombosis and hemostasis in PWH when using both procoagulant and anticoagulant treatments. Generally, PWH could be considered as being naturally anticoagulated when clotting factors are &lt;20 IU/dL, but specific recommendations in patients with very low levels according to the different clinical situations are lacking and mainly based on the anecdotal series. For PWH with baseline clotting factor levels &gt;20 IU/dL in need for any form of antithrombotic therapy, usually treatment without additional clotting factor prophylaxis could be used, but careful monitoring for bleeding is recommended. For antiplatelet treatment, this threshold could be lower with single-antiplatelet agent, but again factor level should be at least 20 IU/dL for dual antiplatelet treatment. In this complex growing scenario, the European Hematology Association in collaboration with the International Society on Thrombosis and Haemostasis, the European Association for Hemophilia and Allied Disorders, the European Stroke Organization, and a representative of the European Society of Cardiology Working Group on Thrombosis has produced this current guidance document to provide clinical practice recommendations for health care providers who care for PWH.
Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results
Authors: Timothy A. Yap, Elisa Fontana, Elizabeth K. Lee, David R. Spigel, Martin Højgaard, Stephanie Lheureux, Niharika B. Mettu, Benedito A. Carneiro, Louise Carter, Ruth Plummer, Gregory M. Cote, Funda Meric-Bernstam, Joseph O’Connell, Joseph D. Schonhoft, Marisa Wainszelbaum, Adrian J. Fretland, Peter Manley, Yi Xu, Danielle Ulanet, Victoria Rimkunas, Mike Zinda, Maria Koehler, Ian M. Silverman, Jorge S. Reis-Filho, Ezra Rosen
Journal: Nature Medicine (2023)

Predictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown to be synthetic lethal with loss of function (LOF) of ataxia telangiectasia-mutated (ATM) kinase, and preclinical studies have identified ATRi-sensitizing alterations in other DNA damage response (DDR) genes. Here we report the results from module 1 of an ongoing phase 1 trial of the ATRi camonsertib (RP-3500) in 120 patients with advanced solid tumors harboring LOF alterations in DDR genes, predicted by chemogenomic CRISPR screens to sensitize tumors to ATRi. Primary objectives were to determine safety and propose a recommended phase 2 dose (RP2D). Secondary objectives were to assess preliminary anti-tumor activity, to characterize camonsertib pharmacokinetics and relationship with pharmacodynamic biomarkers and to evaluate methods for detecting ATRi-sensitizing biomarkers. Camonsertib was well tolerated; anemia was the most common drug-related toxicity (32% grade 3). Preliminary RP2D was 160 mg weekly on days 1-3. Overall clinical response, clinical benefit and molecular response rates across tumor and molecular subtypes in patients who received biologically effective doses of camonsertib (>100 mg d-1) were 13% (13/99), 43% (43/99) and 43% (27/63), respectively. Clinical benefit was highest in ovarian cancer, in tumors with biallelic LOF alterations and in patients with molecular responses. ClinicalTrials.gov registration: NCT04497116 .
The current landscape of software tools for the climate-sensitive infectious disease modelling community
Authors: Sadie J Ryan, Catherine A Lippi, Talia Caplan, Avriel Diaz, Willy Dunbar, Shruti Grover, Simon Johnson, Rebecca Knowles, Rachel Lowe, Bilal A Mateen, Madeleine C Thomson, Anna M Stewart-Ibarra
Journal: The Lancet Planetary Health (2023)

Climate-sensitive infectious disease modelling is crucial for public health planning and is underpinned by a complex network of software tools. We identified only 37 tools that incorporated both climate inputs and epidemiological information to produce an output of disease risk in one package, were transparently described and validated, were named (for future searching and versioning), and were accessible (ie, the code was published during the past 10 years or was available on a repository, web platform, or other user interface). We noted disproportionate representation of developers based at North American and European institutions. Most tools (n=30 [81%]) focused on vector-borne diseases, and more than half (n=16 [53%]) of these tools focused on malaria. Few tools (n=4 [11%]) focused on food-borne, respiratory, or water-borne diseases. The under-representation of tools for estimating outbreaks of directly transmitted diseases represents a major knowledge gap. Just over half (n=20 [54%]) of the tools assessed were described as operationalised, with many freely available online. Climate-sensitive infectious disease modelling is crucial for public health planning and is underpinned by a complex network of software tools. We identified only 37 tools that incorporated both climate inputs and epidemiological information to produce an output of disease risk in one package, were transparently described and validated, were named (for future searching and versioning), and were accessible (ie, the code was published during the past 10 years or was available on a repository, web platform, or other user interface). We noted disproportionate representation of developers based at North American and European institutions. Most tools (n=30 [81%]) focused on vector-borne diseases, and more than half (n=16 [53%]) of these tools focused on malaria. Few tools (n=4 [11%]) focused on food-borne, respiratory, or water-borne diseases. The under-representation of tools for estimating outbreaks of directly transmitted diseases represents a major knowledge gap. Just over half (n=20 [54%]) of the tools assessed were described as operationalised, with many freely available online.
An allosteric pan-TEAD inhibitor blocks oncogenic YAP/TAZ signaling and overcomes KRAS G12C inhibitor resistance
Authors: Thijs J. Hagenbeek, Jason R. Zbieg, Marc Hafner, Rana Mroue, Jennifer A. Lacap, Nicole M. Sodir, Cameron L. Noland, Shervin Afghani, Ayush Kishore, Kamakoti P. Bhat, Xiaosai Yao, Stephen Schmidt, Saundra Clausen, Micah Steffek, Wendy Lee, Paul Beroza, Scott Martin, Eva Lin, Rina Fong, Paola Di Lello, Marta H. Kubala, Michelle N.-Y. Yang, Jeffrey T. Lau, Emily Chan, Alfonso Arrazate, Le An, Elizabeth Levy, Maria N. Lorenzo, Ho-June Lee, Trang H. Pham, Zora Modrusan, Richard Zang, Yi-Chen Chen, Michal Kabza, Musaddeque Ahmed, Jason Li, Matthew T. Chang, Danilo Maddalo, Marie Evangelista, Xin Ye, James J. Crawford, Anwesha Dey
Journal: Nature Cancer (2023)

Abstract The Hippo pathway is a key growth control pathway that is conserved across species. The downstream effectors of the Hippo pathway, YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), are frequently activated in cancers to drive proliferation and survival. Based on the premise that sustained interactions between YAP/TAZ and TEADs (transcriptional enhanced associate domain) are central to their transcriptional activities, we discovered a potent small-molecule inhibitor (SMI), GNE-7883, that allosterically blocks the interactions between YAP/TAZ and all human TEAD paralogs through binding to the TEAD lipid pocket. GNE-7883 effectively reduces chromatin accessibility specifically at TEAD motifs, suppresses cell proliferation in a variety of cell line models and achieves strong antitumor efficacy in vivo. Furthermore, we uncovered that GNE-7883 effectively overcomes both intrinsic and acquired resistance to KRAS (Kirsten rat sarcoma viral oncogene homolog) G12C inhibitors in diverse preclinical models through the inhibition of YAP/TAZ activation. Taken together, this work demonstrates the activities of TEAD SMIs in YAP/TAZ-dependent cancers and highlights their potential broad applications in precision oncology and therapy resistance.
Outcomes and a prognostic classifier in patients with microsatellite instability-high metastatic gastric cancer receiving PD-1 blockade
Authors: Giovanni Randon, Yu Aoki, Romain Cohen, Leonardo Provenzano, Vincenzo Nasca, Samuel J Klempner, Steven B Maron, Riccardo Cerantola, Joseph Chao, Lorenzo Fornaro, Walter Ferrari Bravo, Filippo Ghelardi, Margherita Ambrosini, Paolo Manca, Massimiliano Salati, Akihito Kawazoe, Valerie Zhu, Darren Cowzer, Virginia Genovesi, Sara Lonardi, Kohei Shitara, Thierry André, Filippo Pietrantonio
Journal: Journal for ImmunoTherapy of Cancer (2023)

Subgroup analyses of randomized trials suggest the superiority of immune checkpoint inhibitor-based therapy over chemotherapy in patients with mismatch-repair deficient (dMMR) and/or microsatellite instability-high (MSI-high) advanced gastric or gastroesophageal junction adenocarcinoma. However, these subgroups are small and studies examining prognostic features within dMMR/MSI-high patients are lacking.We conducted an international cohort study at tertiary cancer centers and collected baseline clinicopathologic features of patients with dMMR/MSI-high metastatic or unresectable gastric cancer treated with anti-programmed cell death protein-1 (PD-1)-based therapies. The adjusted HRs of variables significantly associated with overall survival (OS) were used to develop a prognostic score.One hundred and thirty patients were included. At a median follow-up of 25.1 months, the median progression-free survival (PFS) was 30.3 months (95% CI: 20.4 to NA) and 2-year PFS rate was 56% (95% CI: 48% to 66%). Median OS was of 62.5 months (95% CI: 28.4 to NA) and 2-year OS rate was 63% (95% CI: 55% to 73%). Among the 103 Response Evaluation Criteria in Solid Tumors-evaluable patients, objective response rate was 66% and disease control rate 87% across lines of therapy. In the multivariable models, Eastern Cooperative Oncology Group Performance Status of 1 or 2, non-resected primary tumor, presence of bone metastases and malignant ascites were independently associated with poorer PFS and OS. These four clinical variables were used to build a three-category (ie, good, intermediate, and poor risk) prognostic score. Compared with patients with good risk, patients with intermediate risk score had numerically inferior PFS and OS (2-year PFS rate: 54.3% versus 74.5%, HR 1.90, 95% CI: 0.99 to 3.66; 2-year OS rate: 66.8% versus 81.2%, HR 1.86, 95% CI: 0.87 to 3.98), whereas patients with poor risk score had significantly inferior PFS and OS (2-year PFS rate: 10.6%, HR 9.65, 95% CI: 4.67 to 19.92; 2-year OS rate: 13.3%, HR 11.93, 95% CI: 5.42 to 26.23).Overall outcomes with anti-PD-1-based therapies are favorable in MSI-high gastroesophageal adenocarcinomas. However, within this overall favorable subgroup a more accurate prognostication using baseline clinical characteristics might identify patients at higher risk of rapid disease progression who may deserve intensified immunotherapy combination strategies.